Phenotypic Spectrum of SimpsonGolabiBehmel Syndrome in a Series of 42 Cases With a Mutation in GPC3 and Review of the Literature
Phenotypic Spectrum of SimpsonGolabiBehmel Syndrome in a Series of 42 Cases With a Mutation in GPC3 and Review of the Literature
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DOI：
10.1002/ajmg.c.31360
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发表时间：
2013-05-01
影响因子：
3.1
通讯作者：
Toutain, Annick
中科院分区：
文献类型：
--
作者：
Cottereau, Edouard;Mortemousque, Isabelle;Toutain, Annick
GlassonGolabiBehmel综合征（SGBS）是一种罕见的X连锁多发性先天性异常/智力残疾综合征，其特征在于出生前后的过度生长、独特的颅面特征、大头畸形、各种先天性畸形、器官肿大、肿瘤风险增加和轻度/中度智力缺陷。1996年，磷脂酰肌醇蛋白聚糖3（Glypican 3，GPC 3）被鉴定为SGBS的主要致病基因，但突变检出率仅为28 - 70%，提示SGBS的遗传异质性或部分患者可能有其他诊断。这是特别建议的一些报告的非典型病例更严重的疾病。在Golabi和罗森报道的家族中，最近发现了GPC 4的重复，这表明GPC 4可能是SGBS的第二个基因，但尚未报道GPC 4内的点突变。在图尔斯医院的遗传学实验室，十多年来的GPC 3分子检测仅在8.7%的SGBS患者中检测到致病性突变。此外，GPC 4突变尚未确定，因此提出了频繁误诊的问题。为了更好地描述由GPC 3突变引起的SGBS的表型谱，并尝试定义GPC 3分子检测的特定临床标准，我们回顾了在法国提供该检测的两个分子实验室（图尔斯和巴黎）中鉴定的所有GPC 3突变男性病例的临床特征。我们在这里提出的结果分析42例患者属于31个家庭，其中包括5个胎儿和3个死亡的新生儿。(c)2013 Wiley Periodicals，Inc.
SimpsonGolabiBehmel syndrome (SGBS) is a rare X-linked multiple congenital abnormality/intellectual disability syndrome characterized by pre- and post-natal overgrowth, distinctive craniofacial features, macrocephaly, variable congenital malformations, organomegaly, increased risk of tumor and mild/moderate intellectual deficiency. In 1996, Glypican 3 (GPC3) was identified as the major gene causing SGBS but the mutation detection rate was only 2870%, suggesting either genetic heterogeneity or that some patients could have alternative diagnoses. This was particularly suggested by some reports of atypical cases with more severe prognoses. In the family reported by Golabi and Rosen, a duplication of GPC4 was recently identified, suggesting that GPC4 could be the second gene for SGBS but no point mutations within GPC4 have yet been reported. In the genetics laboratory in Tours Hospital, GPC3 molecular testing over more than a decade has detected pathogenic mutations in only 8.7% of individuals with SGBS. In addition, GPC4 mutations have not been identified thus raising the question of frequent misdiagnosis. In order to better delineate the phenotypic spectrum of SGBS caused by GPC3 mutations, and to try to define specific clinical criteria for GPC3 molecular testing, we reviewed the clinical features of all male cases with a GPC3 mutation identified in the two molecular laboratories providing this test in France (Tours and Paris). We present here the results of the analysis of 42 patients belonging to 31 families and including five fetuses and three deceased neonates. (c) 2013 Wiley Periodicals, Inc.